title: Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase.
abstract: Recent findings suggest important roles for nuclear organization in gene expression. In contrast, little is known about how nuclear organization contributes to genome stability. Epistasis analysis (E-MAP) using DNA repair factors in yeast indicated a functional relationship between a nuclear pore subcomplex and Slx5/Slx8, a small ubiquitin-like modifier (SUMO)-dependent ubiquitin ligase, which we show physically interact. Real-time imaging and chromatin immunoprecipitation confirmed stable recruitment of damaged DNA to nuclear pores. Relocation required the Nup84 complex and Mec1/Tel1 kinases. Spontaneous gene conversion can be enhanced in a Slx8- and Nup84-dependent manner by tethering donor sites at the nuclear periphery. This suggests that strand breaks are shunted to nuclear pores for a repair pathway controlled by a conserved SUMO-dependent E3 ligase.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nagai
authors.forename: Karine
authors.initials: K
authors.lastname: Dubrana
authors.forename: Monika
authors.initials: M
authors.lastname: Tsai-Pflugfelder
authors.forename: Marta B
authors.initials: MB
authors.lastname: Davidson
authors.forename: Tania M
authors.initials: TM
authors.lastname: Roberts
authors.forename: Grant W
authors.initials: GW
authors.lastname: Brown
authors.forename: Elisa
authors.initials: E
authors.lastname: Varela
authors.forename: Florence
authors.initials: F
authors.lastname: Hediger
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
mesh_terms: D047369:Chromatin Immunoprecipitation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005785:Gene Conversion; D005800:Genes, Fungal; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007700:Kinetics; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C097894:NUP84 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C515574:Slx8 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae; C037725:SCEI protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific; C515573:Slx5 protein, S cerevisiae